The Neural Basis of Relational Memory Deficits in Schizophrenia

Öngür, Döst; Cullen, Thomas J.; Wolf, Daniel H.; Rohan, Michael L.; Barreira, Paul; Zalesak, Martin; Heckers, Stephan

doi:10.1001/archpsyc.63.4.356

Cited by 122 publications

(92 citation statements)

References 72 publications

(93 reference statements)

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“…The hippocampus is dysfunctional in schizophrenia (Weiss, 2003; Ongür, 2006; Ragland, 2001; Ledoux, 2013; Heckers, and Konradi, 2010). Meta-analyses have concluded that schizophrenia is associated with memory impairment (Heinrichs, and Zakzanis, 1998; Aleman, 1999) and that hippocampal recruitment is impaired during the performance of memory tasks (Weiss, 2003; Heckers, 1998).…”

Section: Introductionmentioning

confidence: 99%

Increased hippocampal CA1 cerebral blood volume in schizophrenia

Talati

Rane

Köse

et al. 2014

NeuroImage: Clinical

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Hippocampal hyperactivity has been proposed as a biomarker in schizophrenia. However, there is a debate whether the CA1 or the CA2/3 subfield is selectively affected. We studied 15 schizophrenia patients and 15 matched healthy control subjects with 3T steady state, gadolinium-enhanced, absolute cerebral blood volume (CBV) maps, perpendicular to the long axis of the hippocampus. The subfields of the hippocampal formation (subiculum, CA1, CA2/3, and hilus/dentate gyrus) were manually segmented to establish CBV values. Comparing anterior CA1 and CA2/3 CBV between patients and controls revealed a significant subfield-by-diagnosis interaction. This interaction was due to the combined effect of a trend of increased CA1 CBV (p = .06) and non-significantly decreased CA2/3 CBV (p = 0.14) in patients relative to healthy controls. These results support the emerging hypothesis of increased hippocampal activity as a biomarker of schizophrenia and highlight the importance of subfield-level investigations.

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Section: Introductionmentioning

confidence: 99%

Increased hippocampal CA1 cerebral blood volume in schizophrenia

Talati

Rane

Köse

et al. 2014

NeuroImage: Clinical

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“…Recent studies have attempted to use relational mnemonic tasks, which are specific to hippocampus, to assess hippocampal function in schizophrenia (Coleman et al, 2010; Öngür et al, 2006; Hanlon et al, 2005, 2006; Titone et al, 2004). One of these tasks is the transverse patterning (TP) problem, which involves a completely overlapping set of relationships among stimuli.…”

Section: (1) Introductionmentioning

confidence: 99%

Bilateral hippocampal dysfunction in schizophrenia

et al. 2011

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The hippocampus has long been known to be important for memory, with the right hippocampus particularly implicated in nonverbal/visuo-spatial memory and left in verbal/narrative or episodic memory. Despite this hypothesized lateralized functional difference, there has not been a single task that has been shown to activate both the right and left hippocampus differentially, dissociating the two, using neuroimaging. The transverse patterning (TP) task is a strong candidate for this purpose, as it has been shown in human and nonhuman animal studies to theoretically and empirically depend on the hippocampus. In TP, participants choose between stimuli presented in pairs, with the correct choice being a function of the specific pairing. In this project, TP was used to assess lateralized hippocampal function by varying its dependence on verbal material, with the goal of dissociating the two hippocampi. Magnetoencephalographic (MEG) data were collected while controls performed verbal and nonverbal versions of TP in order to verify and validate lateralized activation within the hippocampi. Schizophrenia patients were evaluated to determine whether they exhibited a lateralized hippocampal deficit. As hypothesized, patients’ mean level of behavioral performance was poorer than controls’ on both verbal and nonverbal TP. In contrast, patients had no decrement in performance on a verbal and nonverbal non-hippocampal-dependent matched control task. Also, controls but not patients showed more right hippocampal activation during nonverbal TP and more left hippocampal activation during verbal TP. These data demonstrate the capacity to assess lateralized hippocampal function and suggest a bilateral hippocampal behavioral and activation deficit in schizophrenia.

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“…Considerable evidence suggests that individuals with schizophrenia display subtle, but consistent, memory impairments [1, 2]. However, individuals with schizophrenia are not impaired on all forms of memory [1, 3].…”

Section: Introductionmentioning

confidence: 99%

“…However, individuals with schizophrenia are not impaired on all forms of memory [1, 3]. Furthermore, the effect of treatment on memory impairments in schizophrenia remains poorly understood at both the cognitive and neurobiological levels.…”

Section: Introductionmentioning

confidence: 99%

“…Reductions in hippocampal volume [10, 11], increases in hippocampal perfusion (e.g., rCBF) [12, 13], and reductions in task-associated activations in the hippocampus [14, 15] are found in schizophrenia, along with impaired performance on hippocampal-dependent memory tasks [1, 2]. A particularly strong link has been found between hippocampal function and memory generalization in schizophrenia using a transitive inference paradigm [1, 2]. Transitive inference is a form of hippocampal-dependent generalization in which learned information is used to later guide logical inferences.…”

Section: Introductionmentioning

confidence: 99%

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Learning and Generalization in Schizophrenia: Effects of Disease and Antipsychotic Drug Treatment

Shohamy

Mihalakos

Chin

et al. 2010

Biological Psychiatry

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Background Schizophrenia involves alterations in hippocampal function. The implications of these alterations for memory function in the illness remain poorly understood. Furthermore, it remains unknown how memory is impacted by drug treatments for schizophrenia. The goal of this study was to delineate specific memory processes that are disrupted in schizophrenia and explore how they are affected by medication. We specifically focus on memory generalization - the ability to flexibly generalize memories in novel situations. Methods Individuals with schizophrenia (n=56) and healthy controls (n=20) were tested on a computerized memory generalization paradigm. Participants first engage in trial-by-error associative learning. They are then asked to generalize what they learned by responding to novel stimulus combinations. Individuals with schizophrenia were tested on or off anti-psychotic medication, using a between-subject design that eliminates concerns about learning-set effects. Results Individuals with schizophrenia were selectively impaired in their ability to generalize knowledge, despite having intact learning and memory accuracy. This impairment was found only in individuals tested off medication. Individuals tested on medication generalized almost as well as healthy controls. This between-group difference was selective to memory generalization. Conclusion These findings suggest that individuals with schizophrenia have a selective alteration in the ability to flexibly generalize past experience towards novel learning environments. This alteration is unaccompanied by global memory defect. Additionally, the results indicate a robust generalization difference based on medication status. These results suggest that hippocampal abnormalities in schizophrenia may be alleviated with anti-psychotic medication, with important implications for understanding adaptive memory-guided behavior.

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The Neural Basis of Relational Memory Deficits in Schizophrenia

Abstract: Schizophrenia is characterized by a specific deficit of relational memory, which is associated with impaired function of the parietal cortex and hippocampus. Abnormal relational memory may be at the core of 2 prominent features of schizophrenia, ie, cognitive deficits and psychosis.

Cited by 122 publications

References 72 publications

Increased hippocampal CA1 cerebral blood volume in schizophrenia

Increased hippocampal CA1 cerebral blood volume in schizophrenia

Bilateral hippocampal dysfunction in schizophrenia

Learning and Generalization in Schizophrenia: Effects of Disease and Antipsychotic Drug Treatment

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